Spinal fusion, also known as spondylodesis or spondylosyndesis, is a surgical treatment method used for the treatment of various morbidities such as degenerative disc disease, spondylolisthesis (slippage of a vertebra), spinal stenosis, scoliosis, fracture, infection or tumor. The aim of the spinal fusion procedure is to reduce instability and thus pain. Patients requiring spinal fusion have either neurological deficits or severe pain which has not responded to conservative treatment. Spinal fusion is achieved by instrumentation to stop movement between the vertebrae and involves removal of the intervertebral disc, laminectomy, roughening of the bone surfaces that are required to be fused and application of a material that stimulates bone growth between adjacent vertebrae. It is estimated that each year in the US alone, approximately 500,000 spinal fusion procedures are performed.
The spine has three main segments: the cervical spine, the thoracic spine, and the lumbar spine. The cervical spine is the upper part of the spine, i.e., the neck, and it is made up of seven vertebrae. The thoracic spine is the center part of the spine, and it is made up of 12 vertebrae. The lumbar spine is the lower portion of the spine. It is usually made up of five vertebrae; however, some people have six lumbar vertebrae. Spinal fusion is done most commonly in the lumbar region of the spine, but it is also used to treat problems in the cervical and, more rarely, thoracic spine.
There are two types of spinal fusion, which may be used either alone or in conjunction with each other: (i) posterolateral fusion, which places the material that stimulates bone growth (i.e. the bone graft or bone graft substitutes) on the spinal gutter in the back of the spine. These vertebrae are then fixed in place with screws and or wire through the pedicles of each vertebra attaching to a metal rod on each side of the vertebrae and the bone bridge is formed between the transverse processes of the spine; (ii) Interbody fusion, which places the bone graft or bone graft substitute between the vertebra in the area usually occupied by the intervertebral disc. In preparation for the spinal fusion, the disc is removed entirely. A device, the spinal fusion cage, may be placed between the vertebra to maintain spine alignment and disc height. The interbody cage may be made from synthetic polymers, titanium or other metals or bone. The fusion, i.e. bone bridge, occurs between the endplates of the vertebrae. Fusion rates are usually higher with interbody fusion than with posterolateral fusion.
In most cases, the fusion is augmented by a process called fixation, i.e., the placement of metallic screws (pedicle screws often made from titanium), rods or plates, to stabilize the vertebra to facilitate bone fusion. The main challenge in terms of a clinically successful outcome of a spinal fusion procedure is the need to form bone tissue instead of the original type of tissue in the space between the vertebrae. The original type of tissue in case of interbody fusion is a disc and in the case of a posterolateral fusion, it is muscle tissue. As the bone has to grow and replace a different tissue type, there is a need to create an appropriate environment to trigger and promote bone formation in this area.
A bone graft is needed to create the appropriate environment in order for a solid bone bridge to form between the vertebrae. Currently, bone grafts and a variety of bone graft substitutes are used in spinal fusion, with mixed clinical outcomes. A variety of materials may serve as bone grafts or bone graft substitutes, including autografts (harvested from the iliac crest of the patient's body), allografts, demineralised bone matrix, and various synthetic materials. The synthetic materials include calcium phosphates or hydroxyapatites, stem cell containing products which combine stem cells with one of the other classes of bone graft substitutes, and as the latest generation of bone graft substitutes, growth factor containing matrices such as INFUSE® (rhBMP-2-containing bone graft) from Medtronic Sofamor Daniek, Inc. Autograft is the gold standard in this indication because of efficacy and safety. However, due to limited supply of a patient's own bone, the risk of donor site pain and morbidity (blood loss, infection) in combination with long hospital stays and operation time, there has been a continued search for bone graft substitutes to replace autologous bone. Growth factor containing matrices, for example, INFUSE®, have demonstrated equivalent fusion rates to autograft and have therefore had significant impact on the market. However, there are disadvantages associated with this product. In addition to the expensive production process of the BMP (bone morphogenetic protein), the protein is delivered from a collagen matrix in high concentration. Collagen matrices from bovine origin carry the risks associated with xenogenic materials, i.e. disease transmission, and show poor handling properties in the surgical procedure, e.g., they are not moldable to closely fit to the shape of the injury or fusion site. Further, the high concentration of BMPs delivered to the body can lead to calcification of organs or to bone formation in other parts of the body, so called ectopic bone formation. In particular, several complications related to the use of BMP-2 in spinal fusion have been reported (e.g., neurological complications induced by exuberant bone formation, as well as respiratory complications due to inflammatory response/swelling around the application site) (Epstein, Surgical Neurology International, 2:10 (2011)). In July 2008 the FDA issued a safety notice relating to the use of INFUSE® in the cervical spine.
It is an object of the present invention to provide a bone graft substitute which effectively fuses vertebrae in spinal fusion procedures and is safer to use than the currently available bone graft substitutes.
It is a further object of the present invention to provide a bone graft substitute that is easy to prepare and apply (i.e., allows for easy handling) during an operation procedure.
It is still a further object of the present invention to provide a bone graft substitute that allows the application of the product during operation without additional damage to the surrounding tissue.
It is still an object of the present invention to provide an improved method for spinal fusion.
It is also an object of this invention to provide a kit for use in treating spinal fusion.
It is also an object of this invention to provide an improved fusion cage for spinal fusion, in particular for interbody spinal fusion.